Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer.

The efficacy and safety of trastuzumab deruxtecan in patients with no previous therapy for HER2-positive advanced or metastatic breast cancer are unclear.

对于未接受过治疗的HER2阳性晚期或转移性乳腺癌患者，Trastuzumab deruxtecan的疗效和安全性尚不明确。

Methods

We conducted a phase 3 trial involving patients with HER2-positive advanced or metastatic breast cancer and no previous chemotherapy or HER2-directed therapy for metastatic disease.

我们进行了一项涉及HER2阳性晚期或转移性乳腺癌患者的III期试验，这些患者之前没有接受过化疗或针对转移性疾病的HER2导向治疗。

Patients were randomly assigned in a 1:1:1 ratio to receive trastuzumab deruxtecan plus pertuzumab; trastuzumab deruxtecan plus placebo; or a taxane, trastuzumab, and pertuzumab (THP).

患者按1:1:1的比例随机分配，分别接受曲妥珠单抗德曲妥珠单抗加帕妥珠单抗；曲妥珠单抗德曲妥珠单抗加安慰剂；或紫杉烷、曲妥珠单抗和帕妥珠单抗（THP）。

The primary end point was progression-free survivalas assessed by blinded independent central review.

主要终点是通过盲法独立中央审查评估的无进展生存期。

Secondary end points included objective response, duration of response, and safety.

次要终点包括客观缓解率、缓解持续时间以及安全性。

Results

For this prespecified interim analysis, data for trastuzumab deruxtecan plus pertuzumab and for THP are reported; data for trastuzumab deruxtecan plus placebo remain blinded until the final analysis of progression-free survival. At the data-cutoff date (February 26, 2025), the median progression-free survivalwas 40.7 months with trastuzumab deruxtecan plus pertuzumab (383 patients) and 26.9 months with THP (387 patients) (hazard ratiofor progression or death, 0.56; 95% confidence interval[CI], 0.44 to 0.71; P<0.00001 [P-value boundary for superiority, 0.00043]).

在此次预先设定的中期分析中，报告了曲妥珠单抗德曲妥珠联合帕妥珠单抗和THP的数据；曲妥珠单抗德曲妥珠联合安慰剂的数据将在无进展生存期的最终分析之前保持盲态。截至数据截止日期（2025年2月26日），曲妥珠单抗德曲妥珠联合帕妥珠单抗的中位无进展生存期为40.7个月（383名患者），而THP为26.9个月（387名患者）（进展或死亡的风险比为0.56；95%置信区间[CI]，0.44至0.71；P<0.00001 [优越性P值界限，0.00043]）。

The incidenceof a confirmed response was 85.1% with trastuzumab deruxtecan plus pertuzumab and 78.6% with THP (complete responses in 15.1% and 8.5%, respectively), with a median duration of response of 39.2 months and 26.4 months.

曲妥珠单抗德曲妥珠联合帕妥珠单抗的确认反应发生率为85.1%，而THP为78.6%（分别有15.1%和8.5%的完全缓解），反应持续时间的中位数分别为39.2个月和26.4个月。

Safety was consistent with the known profiles of the individual treatments.

安全性与各单独治疗的已知特征一致。

The incidenceof grade 3 or higher adverse events was 63.5% with trastuzumab deruxtecan plus pertuzumab and 62.3% with THP; the most common were neutropenia, hypokalemia, and anemia with trastuzumab deruxtecan plus pertuzumab and neutropenia, leukopenia, and diarrhea with THP.

3级或更高级别的不良事件发生率为：trastuzumab deruxtecan联合pertuzumab组为63.5%，THP组为62.3%；最常见的不良事件分别是：trastuzumab deruxtecan联合pertuzumab组的中性粒细胞减少症、低钾血症和贫血，以及THP组的中性粒细胞减少症、白细胞减少症和腹泻。

Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.1% of patients receiving trastuzumab deruxtecan plus pertuzumab (grade 1 or 2 in 44 patients and grade 5 [death] in 2 patients) and in 1.0% of those receiving THP (all grade 1 or 2).

在接受曲妥珠单抗德曲妥珠加帕妥珠单抗治疗的患者中，有12.1%发生了药物相关的间质性肺病或肺炎（其中44名患者为1级或2级，2名患者为5级[死亡]），而在接受THP治疗的患者中，这一比例为1.0%（均为1级或2级）。

Conclusions

Trastuzumab deruxtecan plus pertuzumab led to a significantly lower risk of progression or death than THP when used as first-line treatment for HER2-positive advanced or metastatic breast cancer, with no new safety signals.

当曲妥珠单抗德曲妥珠加帕妥珠单抗作为HER2阳性晚期或转移性乳腺癌的一线治疗时，与THP相比，其进展或死亡风险显著降低，且未出现新的安全信号。

(Funded by AstraZeneca and Daiichi Sankyo; DESTINY-Breast09 ClinicalTrials.gov number, NCT04784715.).

(由阿斯利康和第一三共资助; DESTINY-Breast09 ClinicalTrials.gov编号, NCT04784715.)。